Peracetic acid indicators and methods of use

ABSTRACT

The present invention provides a hydrogen peroxide indicator and a peracetic acid indicator that include a substrate on which is disposed an indicator composition that includes at least one of a select group of colorants and a transition metal salt. As a result of exposure to hydrogen peroxide and/or peracetic acid, the colorants change color, and even become colorless, thereby providing an indication of the presence of hydrogen peroxide and/or peracetic acid.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. Ser. No. 10/037,435, filed Dec. 31, 2001, now U.S. Pat. No. 7,192,554, the disclosure of which is incorporated by reference in its entirety herein.

BACKGROUND OF THE INVENTIO-N

Medical instruments, particularly surgical instruments, are typically sterilized prior to use using steam or other sterilizing/disinfecting gases or liquids. A traditional sterilization process uses steam under pressure. Alternative sterilization processes use ethylene oxide or hydrogen peroxide in vapor form as the sterilant.

The use of hydrogen peroxide and other chemical vapor phase sterilization techniques typically involve operating temperatures well below those associated with steam sterilization. These “low temperature” technologies generally operate at temperatures below about 80° C., and often below about 65° C. For hydrogen peroxide sterilization, the sterilized goods are typically available for use shortly after the completion of the sterilization cycle. This is because the decomposition products (e.g., water and oxygen) are nontoxic. The potency of the hydrogen peroxide may be augmented by the presence of electrical energy in the form of an ionizing plasma field.

An alternative sterilization process uses a liquid phase peracetic acid solution. Such sterilization processes may be performed in a sterilization chamber. During a typical sterilization cycle, an article to be sterilized is exposed to a sterilization solution containing, for example, about 2000 parts per million (ppm) to 2500 ppm of peracetic acid. The article is exposed to the solution for a sufficient time at a sufficiently high temperature, e.g., 50° C.-60° C., for the sterilization to be effective.

Sterilization indicators are used to monitor whether a sterilization process has been performed. Sterilization indicators typically include an indicator composition, carried on a substrate, that changes color during the sterilization process. Conventional indicators for hydrogen peroxide, however, often fade upon exposure to light. Thus, there is still a need for suitable indicators that include color change compositions for indicating the sterilization of articles using hydrogen peroxide or peracetic acid.

SUMMARY OF THE INVENTION

The present invention is directed to indicators and methods for detecting the presence of, and for monitoring sterilization processes utilizing, a sterilant, including a hydrogen peroxide and/or a peracetic acid sterilant. The indicators and methods include an indicator including a substrate and an indicator composition disposed thereon, wherein the indicator composition includes at least one colorant that changes color when exposed to a sterilant, at least one binder resin, and at least one salt of a transition metal.

In a preferred embodiment of the invention, the transition metal is selected from the group consisting of Group VB, Group VIII, and Group IB transition metals, and combinations thereof. The sterilization indicators of the present invention preferably include colorants that change color when exposed to hydrogen peroxide and/or peracetic acid. The sterilization indicators of the present invention preferably include a colorant selected from the group of classes of colorants consisting of Methane, Monoazo, Diazo, Triazo, Diazine, Thiazine, Xanthene, Oxazine, Cyanine, Anthraquinone, Benzodifuranone, Styryl, Phthalocyanine, Quinophthalone, Nitro, and Nitroso colorants, and combinations thereof, and/or a colorant selected from the group consisting of Victoria green S extra, Basic blue 41, Basic red 15, Acid green AX986, Keystone soap fluoro green, and Basic red 14 colorants, and combinations thereof. Therefore, a sterilization indicator of the present invention may include a colorant that includes, for instance, a combination of a Methane and a Diazo colorant, a combination of Basic blue 41 and Basic red 15, or a combination of a Methane colorant and Basic blue 41. An even more preferred sterilization indicator includes an indicator composition further including at least one colorant that does not change color when exposed to a sterilant, preferably hydrogen peroxide.

In one embodiment, the present invention is directed to methods and indicators for detecting the presence of hydrogen peroxide, preferably hydrogen peroxide in the vapor phase. The methods and indicators are particularly well suited for monitoring whether a hydrogen peroxide sterilization process has been performed.

In another embodiment, the present invention is directed to methods and indicators for detecting the presence of peracetic acid. The peracetic acid can be in the liquid phase or in the vapor phase. Preferably, the peracetic acid is in the liquid phase. The methods and indicators are well suited for monitoring whether a peracetic acid sterilization process has been performed.

The present invention provides a hydrogen peroxide indicator and a peracetic acid indicator that include a substrate and an indicator composition disposed thereon, wherein the indicator composition includes at least one colorant, at least one metal salt, and at least one binder resin. Preferably, the metal salt is a transition metal salt. More preferably, the transition metal salt includes one or more metals from Groups VIB, VIII, and IB of the Periodic Chart, including iron, copper, cobalt, and chromium. Even more preferably, the transition metal salt includes metals from Groups VIII and IB of the Periodic Chart, including iron, copper, and cobalt, and combinations thereof. Most preferably, the transition metal salt includes iron and/or copper. The salts can include inorganic or organic anions. Examples include chloride, acetate, sulfate, chromate, iodate, molybdate, nitrate, oxalate, citrate, propionate, lactate, malate, tartrate, and benzoate. Preferred anions include chloride, acetate, and sulfate.

In a preferred embodiment, the hydrogen peroxide indicator includes: at least one salt of a transition metal; at least one colorant selected from the group of classes of colorants consisting of Methane, Monoazo, Diazo, Triazo, Diazine, Thiazine, Xanthene, Oxazine, and Anthraquinone colorants, and combinations thereof, and/or at least one colorant selected from the group consisting of Victoria green S extra, Basic blue 41, Basic red 15, Acid green AX986, Keystone soap fluoro green, Basic red 14, and combinations thereof; and at least one binder resin. In a more preferred embodiment, the transition metal salt is selected from the group consisting of a copper salt, a cobalt salt, an iron salt, a chromium salt, and combinations thereof. In an even more preferred embodiment, the transition metal salt is at least one iron salt. In a still more preferred embodiment, the colorant is selected from the group consisting of Patent blue violet, Alkali blue 4B, Victoria pure blue BO, Acid fuchsin sodium salt, Alphazurine A, Methyl violet 2B, Ethyl violet, FD/C blue 1, Brilliant blue R, Lissamine green B, Erioglaucine, Eriochrome black T, Eriochrome blue black B, Cibacron brilliant red 3B, Chromotrope 2B, Amaranth, D&C red No. 33, Bordeaux R, Acid violet 7, Acid violet 5, Plasmocorinth B, Acid Blue 113, Acid red 151, Acid black 24, Acid red 97, Direct red 75, Brilliant crocein MOO, Ponceau SS, Reactive black 5, Arsenazo 111, Direct blue 71, Azocarmine G, Methylene violet 3RAX, Toluidine blue O, Methylene green, Sulforhodamine B, Rhodanine 6G, Violamine R, Nile blue A, Basic blue 3, Brilliant cresyl blue BB, Basic red 15, Alizarin violet 3R, Victoria green S extra, Basic blue 41, Acid green AX986, Keystone soap fluoro green, Basic red 14, D&C green No. 5, and combinations thereof. In an even more preferred embodiment, the colorant is selected from the group consisting of Victoria pure blue BO, Acid fuchsin sodium salt, Alphazurine A, Methyl violet 2B, Ethyl violet, FD/C blue 1, Brilliant blue R, Lissamine green B, Erioglaucine, Eriochrome black T, Eriochrome blue black B, Cibacron brilliant red 3B, Chromotrope 2B, D&C red No. 33, Acid violet 7, Acid violet 5, Plasmocorinth B, Acid blue 113, Acid red 151, Acid black 24, Acid red 97, Direct red 75, Brilliant crocein MOO, Ponceau SS, Reactive black 5, Arsenazo 111, Azocarmine G, Methylene violet 3RAX, Toluidine blue O, Methylene green, Sulforhodamine B, Rhodanine 6G, Violamine R, Nile blue A, Basic blue 3, Brilliant cresyl blue BB, Basic red 15, Alizarin violet 3R, Victoria green S extra, Basic blue 41, Acid green AX986, Keystone soap fluoro green, Basic red 14, D&C green No. 5, and combinations thereof. In a still more preferred embodiment, the hydrogen peroxide indicator includes an indicator composition that further includes at least one colorant that does not change color when exposed to hydrogen peroxide vapor.

In another preferred embodiment, the hydrogen peroxide indicator includes a substrate and an indicator composition disposed thereon, wherein the indicator composition includes: at least one salt of cobalt, copper, chromium, and combinations thereof; at least one colorant that changes color when exposed to hydrogen peroxide vapor; and at least one binder resin. In a preferred embodiment, the salt is selected from the group consisting of cobalt chloride, cobalt acetate, cupric chloride, cupric sulfate, cupric acetate, chromium potassium sulfate, and combinations thereof. In another preferred embodiment, the colorant is selected from the group of classes of colorants consisting of Methane, Monoazo, Diazo, Triazo, Diazine, Thiazine, Cyanine, Xanthene, Oxazine, and Anthraquinone colorants, and combinations thereof, and/or the colorant is selected from the group consisting of Victoria green S extra, Basic blue 41, Basic red 15, Acid green AX986, Keystone soap fluoro green, Basic red 14, and combinations thereof. In a further preferred embodiment, the indicator composition additionally includes at least one colorant that does not change color when exposed to hydrogen peroxide.

In another preferred embodiment, the hydrogen peroxide indicator includes a substrate and an indicator composition disposed thereon, wherein the indicator composition includes at least one cobalt salt, at least one colorant that changes color when exposed to hydrogen peroxide vapor, and at least one binder resin. In a more preferred embodiment, the colorant is selected from the group of classes of colorants consisting of Methane, Monoazo, Diazo, Oxazine, and Anthraquinone colorants, and combinations thereof. In an even more preferred embodiment, the colorant is selected from the group consisting of Patent blue violet, Aniline blue, Erioglaucine, Arsenazo 1, Acid blue 92, Eriochrome blue black B, Congo red, Acid blue 29, Nile blue A, Reactive blue 2, Basic red 15, D&C green No. 5, and combinations thereof.

In another preferred embodiment, the hydrogen peroxide indicator includes a substrate and an indicator composition disposed thereon, wherein the indicator composition includes at least one copper salt, at least one colorant that changes color when exposed to hydrogen peroxide vapor, and at least one binder resin. In a more preferred embodiment, the colorant is selected from the group of classes of colorants consisting of Methane, Monoazo, Diazo, Triazo, Diazine, Thiazine, Xanthene, Oxazine, Cyanine, and Anthraquinone colorants, and combinations thereof, and/or the colorant is selected from the group consisting of Victoria green S extra, Basic blue 41, Basic red 15, Acid green AX986, Keystone soap fluoro green, Basic red 14, and combinations thereof. In an even more preferred embodiment, the colorant is selected from the group consisting of Alphazurine A, Methyl violet 2B, Ethyl violet, FD/C blue 1, Brilliant blue R, Lissamine green B, Erioglaucine, Victoria pure blue BO, Acid fuchsin sodium salt, Patent blue violet, Guinea green B, Coomassie violet R 150, Mordant brown 48, Chromotrope 2B, D&C red No. 33, Bordeaux R, Acid violet 7, Acid violet 5, Plasmocorinth, Acid red 151, Acid blue 29, Acid black 24, Acid red 97, Direct red 75, Brilliant crocein MOO, Ponceau SS, Reactive black 5, Arsenazo 111, Direct blue 71, Azocarmine G, Methylene violet 3RAX, Toluidine blue O, Azure B, Methylene green, Sulforhodamine B, Rhodanine 6G, Violamine R, Nile blue A, Basic blue 3, Brilliant cresyl blue BB, Quinaldine red, Basic red 15, Alizarin violet 3R, Reactive blue 2, Victoria green S extra, Basic blue 41, Acid green AX986, Keystone soap fluoro green, Basic red 14, D&C green No. 5, Fast green FCF, and combinations thereof. In a still more preferred embodiment, the colorant is selected from the group of classes of colorants consisting of Methane, Monoazo, Diazo, Diazine, Thiazine, Xanthene, Oxazine, and Cyanine colorants, and combinations thereof, and/or the colorant is selected from the group consisting of Victoria green S extra, Basic blue 41, Basic red 15, Acid green AX986, Keystone soap fluoro green, Basic red 14, and combinations thereof. In a most preferred embodiment, the colorant is selected from the group consisting of Alphazurine A, Methyl violet 2B, Ethyl violet, FD/C blue 1, Brilliant blue R, Lissamine green B, Erioglaucine, Victoria pure blue BO, Acid fuchsin sodium salt, Coomassie violet R 150, Mordant brown 48, Acid violet 5, Plasmocorinth, Acid red 151, Acid blue 29, Acid black 24, Acid red 97, Direct red 75, Arsenazo 111, Azocarmine G, Methylene violet 3RAX, Toluidine blue O, Methylene green, Rhodanine 6G, Basic blue 3, Brilliant cresyl blue BB, Quinaldine red, Basic red 15, Reactive blue 2, Victoria green S extra, Basic blue 41, Keystone soap fluoro green, Basic red 14, D&C green No. 5, and combinations thereof.

In another preferred embodiment, the hydrogen peroxide indicator includes a substrate and an indicator composition disposed thereon, wherein the indicator composition includes at least one chromium salt, at least one colorant that changes color when exposed to hydrogen peroxide vapor, and at least one binder resin. In a more preferred embodiment, the colorant is selected from the group of classes of colorants consisting of Methane, Monoazo, Diazo, and Cyanine colorants, and combinations thereof. In an even more preferred embodiment, the colorant is selected from the group consisting of Ethyl violet, Eriochrome black T, Eriochrome blue black B, Congo red, Acid blue 113, Quinaldine red, and combinations thereof. In a still more preferred embodiment, the colorant is selected from the group consisting of Ethyl violet, Eriochrome black T, Eriochrome blue black B, Acid blue 113, Quinaldine red, and combinations thereof.

In another embodiment, the present invention provides a peracetic acid indicator that includes a substrate and an indicator composition disposed thereon, wherein the indicator composition includes: at least one transition metal salt; at least one colorant selected from the group of classes of colorants consisting of Monoazo and Diazo colorants, and combinations thereof, and/or at least one colorant selected from the group consisting of Victoria green S extra, Basic blue 41, Basic red 15, Acid green AX986, Keystone soap fluoro green, Basic red 14, and combinations thereof; and at least one binder resin. In a preferred embodiment the indicator composition further includes at least one colorant that does not change color when exposed to peracetic acid.

In a preferred embodiment, the peracetic acid indicator includes a substrate and an indicator composition disposed thereon, wherein the indicator composition includes: at least one salt of copper, cobalt, and combinations thereof; at least one colorant that changes color when exposed to peracetic acid, preferably liquid peracetic acid; and at least one binder resin. In a more preferred embodiment, the indicator composition further includes at least one colorant that does not change color when exposed to peracetic acid.

In another preferred embodiment, the peracetic acid indicator includes a substrate and an indicator composition disposed thereon, wherein the indicator composition includes at least one copper salt, at least one colorant that changes color when exposed to peracetic acid, preferably liquid peracetic acid, and at least one binder resin. In a more preferred embodiment, the colorant is selected from the group of classes of colorants consisting of Monoazo and Diazo colorants, and combinations thereof, and/or the colorant is selected from the group consisting of Victoria green S extra, Basic blue 41, Basic red 15, Acid green AX986, Keystone soap fluoro green, Basic red 14, and combinations thereof. In an even more preferred embodiment, the colorant is selected from the group consisting of Acid violet 7, Evans blue, Naphthol blue black, Reactive black 5, Brilliant black BN, Azocarmine B, and combinations thereof.

In another preferred embodiment, the peracetic acid indicator includes a substrate and an indicator composition disposed thereon, wherein the indicator composition includes at least one cobalt salt, at least one colorant that changes color when exposed to peracetic acid, preferably liquid peracetic acid, and at least one binder resin. In a more preferred embodiment, the colorant is selected from the group of classes of colorants consisting of Monoazo and Diazo colorants, and combinations thereof. In an even more preferred embodiment, the colorant is selected from the group consisting of Cibacron brilliant red 3B, Evans blue, Reactive black 5, Brilliant black BN, and combinations thereof The invention also provides methods of monitoring a sterilization process, including a hydrogen peroxide sterilization process and a peracetic acid sterilization process. These methods include: providing an indicator including an indicator composition including at least one salt of a transition metal, at least one colorant that changes color when exposed to a sterilant, and at least one binder resin; providing an article to be sterilized; and exposing the article to be sterilized and the indicator to a sterilant. The sterilant preferably includes hydrogen peroxide, preferably hydrogen peroxide vapor and/or peracetic acid, preferably liquid peracetic acid.

A method of monitoring a hydrogen peroxide sterilization process of the present invention includes: providing a hydrogen peroxide indicator including a substrate and an indicator composition disposed thereon that includes at least one salt of a transition metal, at least one colorant selected from the group of classes of colorants consisting of Methane, Monoazo, Diazo, Triazo, Diazine Thiazine, Cyanine, Xanthene, Oxazine, Anthraquinone, Benzodifuranone, Styryl, Phthalocyanine, Quinophthalone, Nitro, and Nitroso colorants, and combinations thereof, and/or at least one colorant selected from the group consisting of Victoria green S extra, Basic blue 41, Basic red 15, Acid green AX986, Keystone soap fluoro green, Basic red 14, and combinations thereof, and at least one binder resin; providing an article to be sterilized; and exposing the hydrogen peroxide indicator and the article to be sterilized to hydrogen peroxide vapor. In a more preferred method, the salt of a transition metal is selected from the group consisting of cupric chloride, ferrous chloride, cobalt chloride, cobalt acetate, cupric sulfate, ferrous sulfate, chromium potassium sulfate, cupric acetate, and combinations thereof. In an even more preferred method, the indicator composition further includes a colorant that does not change color when exposed to hydrogen peroxide vapor.

In a preferred method of the present invention, the method includes: providing a hydrogen peroxide indicator including a substrate and an indicator composition disposed thereon that includes at least one salt of copper, chromium, iron, cobalt, and combinations thereof, at least one colorant that changes color when exposed to hydrogen peroxide vapor, and at least one binder resin; providing an article to be sterilized; and exposing the hydrogen peroxide indicator and the article to be sterilized to hydrogen peroxide vapor. In a more preferred method, the colorant is selected from the group of classes of colorants consisting of Methane, Monoazo, Diazo, Triazo, Diazine, Thiazine Cyanine, Xanthene, Oxazine, and Anthraquinone colorants, and combinations thereof, and/or the colorant is selected from the group consisting of Victoria green S extra, Basic blue 41, Basic red 15, Acid green AX986, Keystone soap fluoro green, Basic red 14, and combinations thereof.

Another preferred method includes providing a hydrogen peroxide indicator including a substrate and an indicator composition disposed thereon that includes at least one cobalt salt, at least one colorant that changes color when exposed to hydrogen peroxide vapor, and at least one binder resin, providing an article to be sterilized, and exposing the hydrogen peroxide indicator and the article to be sterilized to hydrogen peroxide vapor. In a more preferred method, the colorant is selected from the group of classes of colorants consisting of Methane, Monoazo, Diazo, Oxazine, and Anthraquinone colorants, and combinations thereof. In an even more preferred method, the colorant is selected from the group consisting of Patent blue violet, Aniline blue, Erioglaucine, Arsenazo 1, Acid blue 92, Eriochrome blue black B, Congo red, Acid blue 29, Nile blue A, Reactive blue 2, Basic red 15, D&C green No. 5, and combinations thereof.

Another preferred method includes providing a hydrogen peroxide indicator including a substrate and an indicator composition disposed thereon that includes at least one copper salt, at least one colorant that changes color when exposed to hydrogen peroxide vapor, and at least one binder resin, providing an article to be sterilized, and exposing the hydrogen peroxide indicator and the article to be sterilized to hydrogen peroxide vapor. In a more preferred method, the colorant is selected from the group of classes of colorants consisting of Methane, Monoazo, Diazo, Triazo, Diazine, Thiazine, Xanthene, Oxazine, Cyanine, and Anthraquinone colorants, and combinations thereof, and/or the colorant is selected from the group consisting of Victoria green S extra, Basic blue 41, Basic red 15, Acid green AX986, Keystone soap fluoro green, Basic red 14, and combinations thereof. In an even more preferred method, the colorant is selected from the group consisting of Alphazurine A, Methyl violet 2B, Ethyl violet, FD/C blue 1, Brilliant blue R, Lissamine green B, Erioglaucine, Victoria pure blue BO, Acid fuchsin sodium salt, Patent blue violet, Guinea green B, Coomassie violet R 150, Mordant brown 48 Chromotrope 2B, D&C red No. 33, Bordeaux R, Acid violet 7, Acid violet 5, Plasmocorinth, Acid red 151, Acid blue 29, Acid black 24, Acid red 97, Direct red 75, Brilliant crocein MOO, Ponceau SS, Reactive black 5, Arsenazo 111, Direct blue 71, Azocarmine G, Methylene violet 3RAX, Toluidine blue O, Azure B, Methylene green, Sulforhodamine B, Rhodanine 6G, Violamine R, Nile blue A, Basic blue 3, Brilliant cresyl blue BB, Quinaldine red, Basic red 15, Alizarin violet 3R, Reactive blue 2, Victoria green S extra, Basic blue 41, Acid green AX986, Keystone soap fluoro green, Basic red 14, D&C green No. 5, Fast green FCF, and combinations thereof. In a still more preferred method, the colorant is selected from the group consisting of Alphazurine A, Methyl violet 2B, Ethyl violet, FD/C blue 1, Brilliant blue R, Lissamine green B, Erioglaucine, Victoria pure blue BO, Acid fuchsin sodium salt, Coomassie violet R 150, Mordant brown 48, Acid violet 5, Plasmocorinth, Acid red 151, Acid blue 29, Acid black 24, Acid red 97, Direct red 75, Arsenazo 111, Azocarmine G, Methylene violet 3RAX, Toluidine blue O, Methylene green, Rhodanine 6G, Basic blue 3, Brilliant cresyl blue BB, Quinaldine red, Basic red 15, Reactive blue 2, Victoria green S extra, Basic blue 41, Keystone soap fluoro green, Basic red 14, D&C green No. 5, and combinations thereof.

Another preferred method includes providing a hydrogen peroxide indicator including a substrate and an indicator composition disposed thereon that includes at least one iron salt, at least one colorant that changes color when exposed to hydrogen peroxide vapor, and at least one binder resin, providing an article to be sterilized, and exposing the hydrogen peroxide indicator and the article to be sterilized to hydrogen peroxide vapor. In a more preferred method, the colorant is selected from the group of classes of colorants consisting of Methane, Monoazo, Diazo, Triazo, Diazine, Thiazine, Cyanine, Xanthene, Oxazine, and Anthraquinone colorants, and combinations thereof, and/or the colorant is selected from the group consisting of Victoria green S extra, Basic blue 41, Basic red 15, Acid green AX986, Keystone soap fluoro green, Basic red 14, and combinations thereof. In an even more preferred method, the colorant is selected from the group consisting of Patent blue violet, Alkali blue 4B, Victoria pure blue BO, Acid fuchsin sodium salt, Alphazurine A, Methyl violet 2B, Ethyl violet, FD/C blue 1, Brilliant blue R, Lissamine green B, Erioglaucine, Eriochrome black T, Eriochrome blue black B, Cibacron brilliant red 3B, Chromotrope 2B, Amaranth, D&C red No. 33, Bordeaux R, Acid violet 7, Acid violet 5, Plasmocorinth B, Acid blue 113, Acid red 151, Acid black 24, Acid red 97, Direct red 75, Brilliant crocein MOO, Ponceau SS, Reactive black 5, Arsenazo 111, Direct blue 71, Azocarmine G, Methylene violet 3RAX, Toluidine blue O, Methylene green, Sulforhodamine B, Rhodanine 6G, Violamine R, Nile blue A, Basic blue 3, Brilliant cresyl blue BB, Quinaldine red, Basic red 15, Alizarin violet 3R, Victoria green S extra, Basic blue 41, Acid green AX986, Keystone soap fluoro green, Basic red 14, D&C green No. 5, and combinations thereof. In a still more preferred method, the colorant is selected from the group consisting of Victoria pure blue BO, Acid fuchsin sodium salt, Alphazurine A, Methyl violet 2B, Ethyl violet, FD/C blue 1, Brilliant blue R, Lissamine green B, Erioglaucine, Eriochrome black T, Eriochrome blue black B, Cibacron brilliant red 3B, Chromotrope 2B, D&C red No. 33, Acid violet 7, Acid violet 5, Plasmocorinth B, Acid blue 113, Acid red 151, Acid black 24, Acid red 97, Direct red 75, Brilliant crocein MOO, Ponceau SS, Reactive black 5, Arsenazo 111, Azocarmine G, Methylene violet 3RAX, Toluidine blue O, Methylene green, Sulforhodamine B, Rhodanine 6G, Violamine R, Nile blue A, Basic blue 3, Brilliant cresyl blue BB, Basic red 15, Alizarin violet 3R, Victoria green S extra, Basic blue 41, Acid green AX986, Keystone soap fluoro green, Basic red 14, D&C green No. 5, and combinations thereof.

Another preferred method includes providing a hydrogen peroxide indicator including a substrate and an indicator composition disposed thereon that includes at least one chromium salt, at least one colorant that changes color when exposed to hydrogen peroxide vapor, and at least one binder resin, providing an article to be sterilized, and exposing the hydrogen peroxide indicator and the article to be sterilized to hydrogen peroxide vapor. In a more preferred method, the colorant is selected from the group of classes of colorants consisting of Methane, Monoazo, Diazo, and Cyanine colorants, and combinations thereof. In an even more preferred method, the colorant is selected from the group consisting of Ethyl violet, Eriochrome black T, Eriochrome blue black B, Congo red, Acid blue 113, Quinaldine red, and combinations thereof. In a still more preferred method, the colorant is selected from the group consisting of Ethyl violet, Eriochrome black T, Eriochrome blue black B, Acid blue 113, Quinaldine red, and combinations thereof.

A preferred method of monitoring a sterilization process of the present invention includes: providing a peracetic acid indicator including a substrate and an indicator composition disposed thereon that includes at least one salt of a transition metal, at least one colorant selected from the group of classes of colorants consisting of Monoazo, Diazo, Benzodifuranone, Styryl, Phthalocyanine, Quinophthalone, Nitro, and Nitroso colorants, and combinations thereof, and/or at least one colorant selected from the group consisting of Victoria green S extra, Basic blue 41, Basic red 15, Acid green AX986, Keystone soap fluoro green, Basic red 14, and combinations thereof, and at least one binder resin; providing an article to be sterilized; and exposing the peracetic acid indicator and the article to be sterilized to peracetic acid, preferably liquid peracetic acid. In a more preferred method, the salt of a transition metal is selected from the group consisting of cupric acetate, cobalt acetate, cupric sulfate, and combinations thereof.

In a preferred method of the present invention, the method includes: providing a peracetic acid indicator including a substrate and an indicator composition disposed thereon that includes at least one salt of copper, cobalt, and combinations thereof, at least one colorant that changes color when exposed to peracetic acid, and at least one binder resin; providing an article to be sterilized; and exposing the peracetic acid indicator and the article to be sterilized to peracetic acid, preferably liquid peracetic acid. In a more preferred method, the colorant is selected from the group of classes of colorants consisting of Monoazo and Diazo colorants, and combinations thereof, and/or the colorant is selected from the group consisting of Victoria green S extra, Basic blue 41, Basic red 15, Acid green AX986, Keystone soap fluoro green, Basic red 14, and combinations thereof.

In a preferred method of the present invention, the method includes: providing a peracetic acid indicator including a substrate and an indicator composition disposed thereon that includes at least one copper salt, at least one colorant that changes color when exposed to peracetic acid, and at least one binder resin; providing an article to be sterilized; and exposing the peracetic acid indicator and the article to be sterilized to peracetic acid, preferably liquid peracetic acid. In a more preferred method, the colorant is selected from the group of classes of colorants consisting of Monoazo and Diazo colorants, and combinations thereof, and/or the colorant is selected from the group consisting of Victoria green S extra, Basic blue 41, Basic red 15, Acid green AX986, Keystone soap fluoro green, Basic red 14, and combinations thereof. In a still more preferred method, the colorant is selected from the group consisting of Acid violet 7, Evans blue, Naphthol blue black, Reactive black 5, Brilliant black BN, Azocarmine B, and combinations thereof.

In another preferred method of the present invention, the method includes: providing a peracetic acid indicator including a substrate and an indicator composition disposed thereon that includes at least one cobalt salt, at least one colorant that changes color when exposed to peracetic acid, and at least one binder resin; providing an article to be sterilized; and exposing the peracetic acid indicator and the article to be sterilized to peracetic acid preferably liquid peracetic acid. In a more preferred method, the colorant is selected from the group consisting of Monoazo and Diazo colorants and combinations thereof. In a still more preferred method, the colorant is selected from the group consisting of Cibacron brilliant red 3B, Evans blue, Reactive black 5, Brilliant black BN, and combinations thereof.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

In one embodiment, the present invention provides a sterilant indicator that includes a substrate on which is disposed an indicator composition that includes at least one metal salt, preferably a transition metal salt, at least one of a select group of colorants, and at least one binder resin. Preferably, the sterilant is hydrogen peroxide and/or peracetic acid. As a result of exposure to a sterilant, the colorants change color, and even become colorless, thereby providing an indication of the presence of the sterilant and a method for monitoring a sterilization process.

One embodiment of the invention provides a hydrogen peroxide indicator that includes a substrate on which is disposed an indicator composition that includes at least one transition metal salt and at least one of a select group of colorants that changes color when exposed to hydrogen peroxide, and at least one binder resin. As a result of exposure to hydrogen peroxide, the colorants change color, and even become colorless, providing an indication of hydrogen peroxide presence.

In another embodiment, the present invention provides a peracetic acid indicator that includes a substrate on which is disposed an indicator composition that includes at least one metal salt, preferably a transition metal salt, at least one of a select group of colorants that changes color when exposed to peracetic acid, and at least one binder resin. As a result of exposure to peracetic acid, the colorants change color, thereby providing an indication of the presence of peracetic acid.

In particular, the present invention is directed to a system for indicating exposure to a hydrogen peroxide vapor sterilization process or a peracetic acid sterilization process, which may use either liquid peracetic acid or peracetic acid vapor. In one embodiment, the indicator composition includes at least one component that is transformed (typically, chemically transformed) when exposed to hydrogen peroxide vapor such that the color of the composition changes. In another embodiment, the indicator composition includes at least one component that is transformed (typically, chemically transformed) when exposed to liquid peracetic acid and/or peracetic acid vapor, preferably liquid peracetic acid, such that the color of the composition changes. The compositions may include one or more components that change color when exposed to hydrogen peroxide and/or peracetic acid, as well as other components that do not change color when exposed to hydrogen peroxide and/or peracetic acid. The composition preferably includes a polymeric binder resin to aid in applying the composition to a suitable substrate.

Indicators of the present invention are very useful to show when an article has been exposed to hydrogen peroxide and/or peracetic acid. Significantly, indicators of the present invention offer one a simple, yet effective means for indicating when a particular article has been subjected to sterilization using hydrogen peroxide vapor and/or liquid peracetic acid or peracetic acid vapor.

Preferably, the hydrogen peroxide indicator compositions of the present invention undergo a color change when exposed to an atmosphere above an aqueous solution containing 30 weight percent (wt-%) hydrogen peroxide at 50° C. within a period of at least about one hour and/or a color change when exposed to an atmosphere containing about 6 milligrams/liter (mg/l) to about 7 mg/l hydrogen peroxide (in an empty chamber, i.e., without articles to be sterilized) at a pressure of about 8×10² Pascals (Pa) to about 13.3×10² Pa and a temperature of about 45° C. to about 50° C. for a period of at least about 50 minutes, which are typical conditions within an empty commercial hydrogen peroxide plasma sterilizer. More preferably, for use in conventional sterilizers, the hydrogen peroxide indicator compositions of the present invention undergo a color change when exposed to an atmosphere containing about 6 mg/l to about 7 mg/l hydrogen peroxide (in an empty chamber) at a pressure of about 8×10² Pa to about 13.3×10² Pa and a temperature of about 45° C. to about 50° C. for a period of at least about 50 minutes. As used herein, a color change includes a change in color that is detectable by the unaided eye, including becoming colorless.

The peracetic acid indicator compositions of the present invention preferably undergo a color change when exposed to liquid and/or vapor phase peracetic acid. Preferably, the peracetic acid indicators undergo a distinct color change when exposed to an atmosphere containing at least 5% peracetic acid at room temperature for at least 5 to 10 minutes. More preferably, the indicator compositions of the present invention undergo a color change when exposed to liquid peracetic acid at a concentration of between about 100 ppm to about 10,000 ppm at temperatures between about 0° C. to about 100° C. for between about 1 second to about 15 minutes. As used herein, a color change includes a change in color that is detectable by the unaided eye, including becoming colorless.

Preferably, the indicator compositions do not significantly fade upon exposure to room lighting, e.g., fluorescent lighting. More preferably, the indicator compositions do not significantly fade, for example, upon exposure to sunlight through a window for one week or room lighting for two months.

Colorants suitable for use in the indicator compositions of the present invention include colorants classified as Methane, Monoazo, Diazo, Triazo, Diazine, Cyanine, Thiazine, Xanthene, Oxazine, Anthraquinone, Benzodifuranone, Styryl, Phthalocyanine, Quinophthalone, Nitro, and Nitroso colorants, and combinations thereof, and/or colorants including Victoria green S extra, Basic blue 41, Basic red 15, Acid green AX986, Keystone soap fluoro green, and Basic red 14 colorants, and combinations thereof. Suitable colorants for use in the indicator compositions of the present invention further include Alphazurine A, Methyl violet 2B, Ethyl violet, FD/C blue 1, Brilliant blue R, Lissamine green B, Erioglaucine, Patent blue violet, Aniline blue, Victoria pure blue BO, Acid fuchsin sodium salt, Guinea green B, Alkali blue 4B, Coomassie violet R 150, Chromotrope 2B, D & C red No. 33, Bordeaux R, Acid violet 7, Acid violet 5, Plasmocorinth B, Cibacron brilliant red 3B, Amaranth, Arsenazo 1, Acid blue 92, Eriochrome blue black B, Eriochrome black T, Mordant brown 48, Acid black 24, Acid red 97, Direct red 75, Brilliant crocein MOO, Ponceau SS, Reactive black 5, Arsenazo 1 11, Congo red, Acid blue 29, Acid blue 113, Acid red 151, Direct blue 71, Azocarmine G, Methylene violet 3RAX, Toluidine blue O, Methylene green, Azure B, Sulforhodamine B, Rhodanine 6G, Violamine R, Nile blue A, Basic blue 3, Brilliant cresyl blue BB, Quinaldine red, Basic red 15, Alizarin violet 3R, Reactive blue 2, Victoria green S extra, Basic blue 41, Acid green AX986, D & C green No. 5, Keystone soap fluoro green, Basic red 14, Brilliant black BN, Evans blue, Naphthol blue black, Xylidine ponceau 2R, Azocarmine B, and Fast green FCF. Alternative names and Color Index Numbers for these colorants are listed in Tables 1-13 below. Those colorants with classifications and/or Color Index Numbers that are difficult to determine are indicated in the tables as “Not Known.” In this instance, “Not Known” means merely that determination of Colorant Class and/or Color Index Number is difficult, not necessarily that it is entirely unknown in the art. Various combinations of these colorants can be used in the indicator compositions of the present invention. Such mixtures or blends would increase the options available in color changes dramatically.

For hydrogen peroxide indicators, suitable colorants become colorless or change to a different color, detectable by the unaided eye, upon exposure to hydrogen peroxide vapor under conventional sterilization conditions (e.g., 6 mg/l to about 7 mg/l hydrogen peroxide in an empty chamber at a pressure of about 8×10² Pa to about 13.3×10² Pa and a temperature of about 45° C. to about 50° C. for a period of at least about 50 minutes) or to the more concentrated hydrogen peroxide vapors in a desiccator.

Preferably, at least one colorant is present in a hydrogen peroxide indicator composition in an amount sufficient to cause a visibly apparent color change when the composition is exposed to an atmosphere above an aqueous solution containing 30 wt-% hydrogen peroxide at 50° C. within a period of at least about one hour and/or an amount sufficient to cause a color change when exposed to an atmosphere containing about 6 mg/l to about 7 mg/l hydrogen peroxide (in an empty chamber) at a pressure of about 8×10² Pa to about 13.3×10² Pa and a temperature of about 45° C. to about 50° C. for a period of at least about 50 minutes. Generally, the compositions contain about 0.1 wt-% to about 5.0 wt-%, based on the total weight of the composition, of a colorant that changes color upon exposure to hydrogen peroxide.

In effect, the colorant concentration should be such as to allow a clear visual indication of a color change. Preferred are those colorants that show contrast between initial color and the color after exposure to hydrogen peroxide vapor. Examples include hydrogen peroxide indicators including cupric chloride and Alphazurine A, Methyl violet 2B, Ethyl violet, FD/C blue 1, Brilliant blue R, Lissamine green B, Erioglaucine, Victoria pure blue BO, Acid fuchsin sodium salt, Chromotrope 2B, D&C red No. 33, Bordeaux R, Acid violet 7, Acid violet 5, Plasmocorinth B, Acid black 24, Acid red 97, Direct red 75, Brilliant crocein MOO, Ponceau SS, Reactive black 5, Arsenazo 111, Direct blue 71, Azocarmine G, Methylene violet 3RAX, Toluidine blue O, Methylene green, Sulforhodamine B, Rhodanine 6G, Violamine R, Nile blue A, Basic blue 3, Brilliant cresyl blue BB, Quinaldine red, Basic red 15, Alizarin violet 3R, Victoria green S extra, Basic blue 41, Acid green AX986, Keystone soap fluoro green, Basic red 14, D & C green No. 5, and combinations thereof (Tables 1b and 5); hydrogen peroxide indicators including cupric sulfate and Patent blue violet, Guinea green B, Methylene violet 3RAX, Azure B, Basic Red 15, Fast green FCF, and combinations thereof (Table 6); and hydrogen peroxide indicators including cupric acetate and Coomassie violet R 150, Mordant brown 48, Acid red 151, Acid blue 29, Reactive blue 2, and combinations thereof (Table 10).

If at least one colorant that does not change color upon exposure to hydrogen peroxide is used in the indicator compositions of the present invention, it is present, alone or in combination with one or more additional colorants, in an amount sufficient to provide the targeted color intensity, both prior to and subsequent to exposure to hydrogen peroxide vapor. Generally, such compositions contain about 0.1 wt-% to about 5.0 wt-%, based on the total weight of the composition, of a colorant that does not change color upon exposure to hydrogen peroxide.

Such colorants that become substantially colorless after exposure to hydrogen peroxide acid can also be used in combination with other colorants (e.g., dyes or pigments) that do not change color when exposed to hydrogen peroxide to give a chemical indicator with a suitable contrasting color change by subtracting color. For example, an indicator including the metal salt cupric chloride with Cibacron brilliant red 3B (pale pink, Table 1b, No. 15) and Ethyl violet (blue, Table 1b, No. 5) would have a blue green color, as a result of the mixture of pale pink and blue. When exposed to hydrogen peroxide vapor, the Ethyl violet turns colorless (Table 1b, No. 5), leaving the pale pink of the Cibacron brilliant red 3B, which does not change color when exposed to hydrogen peroxide vapor (Table 1b, No. 15).

Preferred are those colorants that have an initial color and turns colorless after exposure to hydrogen peroxide vapor. Examples include hydrogen peroxide indicators including ferrous chloride and Alphazurine A, Methyl violet 2B, Ethyl violet, FD/C blue 1, Brilliant blue R, Lissamine green B, Erioglaucine, Victoria pure blue BO, Acid fuchsin sodium salt, Cibacron brilliant red 3B, Chromotrope 2B, D&C red No. 33, Acid violet 7, Acid violet 5, Plasmocorinth B, Acid black 24, Acid red 97, Direct red 75, Brilliant crocein MOO, Ponceau SS, Reactive black 5, Arsenazo 111, Azocarmine G, Methylene violet 3RAX, Toluidine blue O, Methylene green, Sulforhodamine B, Rhodanine 6G, Violamine R, Nile blue A, Basic blue 3, Brilliant cresyl blue BB, Basic red 15, Alizarin violet 3R, Victoria green S extra, Basic blue 41, Acid green AX986, Keystone soap fluoro green, Basic red 14, D & C green No. 5, and combinations thereof (Tables 2 and 7); hydrogen peroxide indicators including ferrous sulfate and Eriochrome black T, Eriochrome blue black B, Acid blue 113, Acid red 151, and combinations thereof (Table 8); hydrogen peroxide indicators including cupric chloride and Alphazurine A, Methyl violet 2B, Ethyl violet, FD/C blue 1, Brilliant blue R, Lissamine green B, Erioglaucine, Victoria pure blue BO, Acid fuchsin sodium salt, Acid violet 5, Plasmocorinth B, Acid black 24, Acid red 97, Direct red 75, Arsenazo 111, Azocarmine G, Methylene violet 3RAX, Toluidine blue O, Methylene green, Rhodanine 6G, Basic blue 3, Brilliant cresyl blue BB, Quinaldine red, Basic red 15, Victoria green S extra, Basic blue 41, Keystone soap fluoro green, Basic red 14, D & C green No. 5, and combinations thereof (Tables 1b and 5); hydrogen peroxide indicators including cobalt chloride and Patent blue violet, Aniline blue, Arsenazo 1, Acid blue 92, Congo red, Acid blue 29, and combinations thereof (Table 3b); hydrogen peroxide indicators including cobalt acetate and Erioglaucine, Eriochrome blue black B, Nile blue A, Reactive blue 2, Basic red 15, D&C green No. 5, and combinations thereof (Table 4); hydrogen peroxide indicators including cupric sulfate and Methylene violet 3RAX (Table 6); hydrogen peroxide indicators including chromium potassium sulfate and Ethyl violet, Eriochrome black T, Eriochrome blue black B, Acid blue 113, Quinaldine red, and combinations thereof (Table 9); and hydrogen peroxide indicators including cupric acetate and Coomassie violet R 150 (Table 10).

For peracetic acid indicators, suitable colorants change to a different color upon exposure to liquid peracetic acid under conventional sterilization conditions. The peracetic acid indicator compositions of the present invention preferably undergo a color change when exposed to liquid and/or vapor phase peracetic acid. Preferably, the peracetic acid indicators undergo a distinct color change when exposed to an atmosphere containing at least 5% peracetic acid at room temperature for at least 5 to 10 minutes. More preferably, the indicator compositions of the present invention undergo a color change when exposed to liquid peracetic acid at a concentration of between about 100 ppm to about 10,000 ppm at temperatures between about 0° C. to about 100° C. for between about 1 second to about 15 minutes.

Preferably, at least one colorant is present in a peracetic acid indicator composition in an amount sufficient to cause a visibly apparent color change when the composition is exposed in a sterilization chamber to a sterilant including liquid peracetic acid at a concentration of 0.2 percent and a pH of 6.4 for about 12 minutes at a temperature of between about 50° C. to about 56° C. The colorant concentration should be such as to allow a clear visual indication of a color change detectable by the unaided eye. Preferred colorants for peracetic acid indicators are those colorants that show contrast between the initial color and the color after exposure to liquid peracetic acid vapor. Examples include peracetic acid indicators including cupric acetate and Evans blue, Acid violet 7, Naphthol blue black, Reactive black 5, Brilliant black BN, Azocarmine B, and combinations thereof (Table 11); peracetic acid indicators including cobalt acetate and Cibacron brilliant red 3B, Evans blue, Reactive black 5, Brilliant black BN, and combinations thereof (Table 12); and peracetic acid indicators including cupric sulfate and Evans blue, Acid violet 7, Naphthol blue black, Reactive black 5, Brilliant black BN, Azocarmine B, and combinations thereof (Table 13).

Preferably, hydrogen peroxide indicators and peracetic acid indicators of the present invention include a metal salt. Preferably the metal salt is a transition metal salt. More preferably, the metal salt includes one or more metals from Groups VIB, VIII, and IB of the Periodic Chart, which include iron, copper, cobalt, and chromium. Even more preferably, the metal salt includes metals from Groups VIII and IB of the Periodic Chart, which include iron, copper, cobalt, and combinations thereof. Most preferably, the metal salt includes iron and/or copper.

The salts can include inorganic or organic anions. Examples include chloride, acetate, sulfate, chromate, iodate, molybdate, nitrate, oxalate, citrate, propionate, lactate, malate, tartrate, and benzoate. Preferred anions include chloride, acetate, and sulfate.

The indicator composition is generally formulated in the form of a dispersion or solution in water or an organic solvent (preferably, an organic solvent). The composition includes at least one colorant as described above as well as an organic binder resins. A wide variety of suitable binder resins can be used. Examples include synthetic or natural polymers or resins. Suitable binder resins are those that do not interfere with the function of the indicator composition. Examples include cellulose acetate butyrate, cellulose acetate propionate, hydroxypropyl cellulose, nitrocellulose, urethane alkyd, epoxy, alkylated urea- and melamine-formaldehyde, polyamide, styrene butadiene, vinyl, phenolic, shellac, ethyl cellulose, methyl cellulose, acrylic, and ultraviolet and electron beam curable resins. A sufficient amount of binder resin is included in the compositions to provide adequate binding of the composition to a substrate on which it is disposed, while providing the desired rate of color change. Generally, the compositions contain about 20 wt-% to about 40 wt-% of a polymer binder resin, based on the total weight of the composition.

Indicator compositions of the present invention can also include other resins that do not necessarily function as a binder resin. For example, the compositions can include a resin that functions as a dispersing agent, such as Rhoplex I-545, a water based acrylic polymer, available from Rohm and Haas Corp., Philadelphia, Pa., that assists in dispersing the ingredients of the composition in the solvent used in application of the composition to a substrate. Indicator compositions of the present invention can also include opacifying agents such as titanium dioxide, surfactants, plasticizers, antifoam agents, and the like. For certain embodiments, a basic material such as an organic amine (e.g., triethanolamine) can be used to enhance sensitivity of the colorant to the low concentration of hydrogen peroxide in a conventional sterilizer. Typically, such additives are used in no more than about 5 wt-% based on the total weight of the indicator composition.

The compositions are typically applied to a substrate out of a solvent as discussed above. Suitable solvents include water and organic solvents such as ketones, esters, alcohols, and the like. Examples of suitable solvents include methyl ethyl ketone, n-propyl acetate, and isopropanol. The solvent is typically used in an amount of up to about 20 wt-%, based on the total weight of the composition. The indicator composition can be applied to the substrate by a wide variety of techniques, including, for example, printing or coating by flexographic, gravure, screen, or die processes.

The substrate on which the indicator composition is disposed can be any of a wide variety. Typically, suitable substrates include polymeric materials, which may be pigmented or colorless, such as polyester, polyethylene, or polystyrene films, nonwovens, paper, and the like. Preferably, it is a plastic polystyrene backing (commercially available from Plastic Suppliers, Inc., Chicago Heights, Ill.). The substrate may be in the form of a strip of material (e.g., a strip of material having the dimensions 2 cm by 13 cm). Optionally, the composition can be coated as a stripe over the length of the substrate strip. The substrate may also have an adhesive on the surface opposite that on which the indicator composition is disposed. In this way, the indicator may be used as a tape or label for attachment to the article to be sterilized.

The hydrogen peroxide vapor sterilization procedure used is conventional, and is disclosed in, for example, U.S. Pat. Nos. 4,756,882, 4,643,876, 4,956,145, and 5,445,792. Preferably, it is a plasma-based sterilization system.

In general, the article to be sterilized is placed in a sterilization chamber with any of the preferred embodiments of hydrogen peroxide indicator of the invention, and a dose of hydrogen peroxide, which generally comes pre-measured, is delivered to the chamber. Vapor is generated and allowed to fill the container for an appropriate length of time after which the sterilization is complete. The indicator is then inspected for color change. The equipment and the entire procedure generally are controlled electronically. When sterilizing medical instruments, one cycle is often sufficient. The medical instruments are often packaged, with the entire package being placed into the sterilizing compartment. The package allows the hydrogen peroxide to penetrate and effect sterilization of the instruments, while subsequently protecting the instruments from contamination in air. The temperatures used in the process of the present invention are all generally less than 65° C.

The peracetic acid sterilization procedures that may be used are conventional, and are disclosed in, for example, U.S. Pat. Nos. 6,287,518 and 4,892,706. A conventional liquid peracetic acid sterilization procedure is disclosed in U.S. Pat. No. 4,892,706.

In general, the article to be sterilized is placed in a sterilization chamber with any of the preferred embodiments of peracetic acid indicator of the invention. Concentrated peracetic acid is then diluted in a buffer solution to form a sterilant solution, which is introduced to and circulated throughout the sterilization chamber. The article to be sterilized and the indicator are exposed to the sterilant solution for at least approximately 12 minutes at a temperature at or below about 60° C. The sterilization chamber is then drained and rinsed with water. The rinsed article and indicator are removed from the sterilization chamber and the indicator is inspected for color change.

The invention will be illustrated in greater detail by the following specific examples. It is understood that these examples are given by way of illustration and are not meant to limit the disclosure or the claims to follow. All percentages in the examples, and elsewhere in the specification, are by weight unless otherwise specified.

EXAMPLES Control Example A without Metal Salts

Control indicator compositions (Control Indicator Composition A) were prepared by shaking 10 milliliters (ml) of a binder-solution containing 7 wt-% percent of hydroxypropyl cellulose in 9 parts methanol: 1 part water, with approximately 0.1 gram (g) or a sufficient amount of colorant (0.1 wt-% to 5 wt-%) to give a good color in a glass vial. The colorants used to prepare these control indicator compositions are listed in Table 1a.

Example 1 Preparation of Indicator Compositions

Indicator compositions (Indicator Composition 1) listed in Table 1b were prepared by adding 1 drop of a saturated cupric chloride water solution to the control indicator compositions described in Control Example A and shaking in the glass vial.

Coating of Indicator Compositions

Indicator compositions and control indicator compositions were coated on plastic polystyrene backing (commercially available from Plastic Suppliers Inc., Chicago Heights, Ill.) using a number 16 Meyer bar (commercially available from R. D. Specialties, Webster, N.Y.). The coated inks were dried at 50° C. in an oven (commercially available as “Despatch Style V 29” from Despatch Oven Co., Minneapolis, Minn.) for 2 minutes. The coated films were cut using scissors to obtain indicators approximately 2 centimeters (cm) by 13 cm.

Test Method

Each coated indicator composition and coated control indicator composition was placed on an instrument tray lid and exposed to a full Hospital 100 cycle of a hydrogen peroxide plasma sterilization procedure at 45-55° C. in a STERRAD 100SI GMP Sterilizer, obtained from Advanced Sterilization Products Co., Irvine, Calif. During the sterilization procedure a vacuum was drawn in the sterilization chamber for 5-6 minutes until the pressure was reduced to 40.0 Pa. A 1.8 ml aliquot of an aqueous solution of 58-60 percent hydrogen peroxide was then injected into the empty sterilization chamber, yielding an empty chamber concentration of 6-7 mg/l hydrogen peroxide. Hydrogen peroxide vapor was allowed to diffuse throughout the chamber for 44 minutes at 8×10² to 13.3×10² Pa. A vacuum was then drawn, reducing the pressure to 66.7 Pa and removing all detectable hydrogen peroxide vapor from the chamber. A plasma phase was then generated in the chamber by emitting an RF power source at 400 watts and 13.56 MegaHertz (MHz) for about 15-16 minutes at 66.7 Pa, after which the chamber was vented for 3-4 minutes until atmospheric pressure was reached in the chamber. After exposure to the sterilization procedure the indicators were removed from the tray lid and examined for color change. The results for each control indicator composition and indicator composition are described in Table 1 a and Table 1b, respectively.

After the colorants were exposed to a full Hospital 100 cycle of hydrogen peroxide plasma sterilization procedure as described above, most of the control indicator compositions (Table 1a) did not change from their initial color. However, Victoria green S extra became colorless; Basic blue 41, Toluidine blue O, and Arsenazo 111 became lighter; Quinaldine red and Alkali blue 4B became slightly lighter; and Violamine R changed from a light pink to pink/violet (darker).

After cupric chloride was added to the indicator composition, most of the colorants either became colorless or significantly lighter when exposed to hydrogen peroxide plasma as described above (Table 1b). The colorants including cupric chloride that did not change or changed so slightly as to make the change difficult to see with the human eye were Cibacron brilliant red 3B, Amaranth, and Brilliant black BN; Nile blue A changed from light blue to light gray; Bordeaux R changed from light pink to a slightly lighter pink; Direct red 75 changed from almost colorless to colorless; and Ponceau SS changed from pink/beige to light purple/pink.

As demonstrated in Example 2, below (Table 2), the choice of metal ion can affect the color change. For instance an indicator composition including one metal ion can produce a color change in an indicator composition exposed to a sterilant that is different from that of an indicator composition including the same colorant with a different metal ion that is also exposed to a sterilant. Compare, for example, the colorant Chromotrope 2B listed in Table 2, No. 7 (with ferrous chloride) that turns colorless with Chromotrope 2B listed in Table 1b, No. 57 (with cupric chloride) that turns beige.

Example 2 Preparations of Indicator Compositions using Ferrous Chloride

Indicator compositions (Indicator Composition 2, Table 2) were prepared by adding 1 drop of a saturated ferrous chloride water solution to the control indicator compositions described in Control Example A and shaking in the glass vial. The colorants used with the ferrous chloride are listed in Table 2.

Indicator compositions and control indicator compositions were coated on plastic backings and sterilized as described in Example 1.

The results for each control indicator composition (Control Indicator Composition A) and Indicator Composition 2 are shown in Table 1a and Table 2, respectively.

After the addition of ferrous chloride to the control composition, each of the colorants listed in Table 2 either became colorless or significantly lighter when exposed to hydrogen peroxide plasma as described above.

Control Example B without Metal Salts

Control indicator compositions (Control Indicator B, Table 3a) were prepared by shaking 10 milliliters (ml) of a binder solution containing 5 wt-% of hydroxypropyl cellulose in 6 parts methanol: 4 parts water, with approximately 0.1 g or a sufficient amount of colorant (0.1 wt-% to 5 wt-%) to give a good color in a glass vial. The colorants used in the Control Indicator Composition B for Examples 3-10 are listed in Table 3a.

Example 3 Preparation of Indicator Compositions using Cobalt Chloride

A drop of cobalt chloride salt solution containing 1 g of salt to 3.25 g of water was added to the control indicator composition described in Control Example B and shaken in a glass vial. The colorants used with cobalt chloride are listed in Table 3b.

Indicator compositions and control indicator compositions were coated on plastic backings and sterilized as described in Example 1.

The results for each Control Indicator Composition B and Indicator Composition 3 are shown in Table 3a and Table 3b respectively.

After the colorants were exposed to a full Hospital 100 cycle of hydrogen peroxide plasma sterilization procedure as described above, most of the colorants did not change from their initial color. However, Guinea green B became almost colorless; Acid fuchsin sodium salt became lighter; Nile blue A, Arsenazo 1, Basic red 14, Basic red 15, and Alkali blue 4B became slightly lighter; Azure B became significantly lighter, Aniline blue changed from blue to gray/green; Quinaldine red changed from muddy pink to light pink, and Acid blue 92 changed from lilac to light violet.

After the addition of cobalt chloride to the control composition, all of the colorants listed in Table 3b became colorless when exposed to hydrogen peroxide plasma as described above.

Example 4 Preparation of Indicator Compositions using Cobalt Acetate

Indicator compositions were prepared as described in Example 3 except a drop of cobalt acetate salt solution containing 1 g of salt to 3.25 g of water was added to the initial composition and shaken in a glass vial. The colorants used are listed in Table 4

Indicator compositions and control indicator compositions were coated on plastic backings and sterilized as described in Example 1.

The results for each control indicator composition and Indicator Composition 4 are shown in Table 3a and Table 4, respectively.

After the addition of cobalt acetate to the control composition each of the colorants listed in Table 4 became colorless when exposed to hydrogen peroxide plasma as described above.

Example 5 Preparation of Indicator Compositions using Cupric Chloride

Indicator compositions were prepared as described in Example 3 except four drops of cupric chloride salt solution containing 1 g of salt to 13 g of water was added to the initial composition and shaken in a glass vial. The colorants used are listed in Table 5

Indicator compositions and control indicator compositions were coated on plastic backings and sterilized as described in Example 1.

The results for each control indicator composition and Indicator Composition 5 are shown in Table 3a and Table 5, respectively.

After the addition of cupric chloride to the control composition, each of the colorants listed in Table 5 became colorless when exposed to hydrogen peroxide plasma as described above.

Example 6 Preparation of Indicator Compositions using Cupric Sulfate

Indicator compositions were prepared as described in Example 3 except four drops of cupric sulfate salt solution containing 1 g of salt to 13 g of water was added to the initial composition and shaken in a glass vial. The colorants used are listed in Table 6

Indicator compositions and control indicator compositions were coated on plastic backings and sterilized as described in Example 1.

The results for each control indicator composition and Indicator Composition 6 are shown in Table 3a and Table 6, respectively.

The addition of cupric sulfate to the control composition of the colorants listed in Table 6 did not show as dramatic results as the preceding examples. Each colorant changed color when exposed to hydrogen peroxide plasma as described above; however, Azure B became clear, Methylene violet 3RAX became almost colorless, and Basic red 15 became significantly lighter. Patent blue violet changed from green/blue to green/gray; Guinea green B and Fast green FCF changed from green to a mottled green on clear when exposed to hydrogen peroxide plasma.

Example 7 Preparation of Indicator Compositions using Ferrous Chloride

Indicator compositions were prepared as described in Example 3 except a drop of ferrous chloride salt solution containing 1 g of salt to 3.25 g of water was added to the initial composition and shaken in a glass vial. The colorants used are listed in Table 7.

Indicator compositions and control indicator compositions were coated on plastic backings and sterilized as described in Example 1.

The results for each control indicator composition and Indicator Composition 7 are shown in Table 3a and Table 7, respectively.

After the addition of ferrous chloride to the control composition, the colorants listed in Table 7 became colorless when exposed to hydrogen peroxide plasma as described above.

Example 8 Preparation of Indicator Compositions using Ferrous Sulfate

Indicator compositions were prepared as described in Example 3 except four drops of ferrous sulfate salt solution containing 1 g of salt to 13 g of water was added to the initial composition and shaken in a glass vial. The colorants used are listed in Table 8

Indicator compositions and control indicator compositions were coated on plastic backings and sterilized as described in Example 1.

The results for each control indicator composition and Indicator Composition 8 are shown in Table 3a and Table 8, respectively.

After the addition of ferrous sulfate to the control composition, each of the colorants either became colorless, almost colorless, or significantly lighter when exposed to hydrogen peroxide plasma as described above.

Example 9 Preparation of Indicator Compositions using Chromium Potassium Sulfate

Indicator compositions were ready as described in Example 3 except a drop of chromium potassium sulfate salt solution containing 1 g of salt to 3.25 g of water was added to the initial composition and shaken in a glass vial. The colorants used are listed in Table 9. Indicator compositions and control indicator compositions were coated on plastic backings and sterilized as described in Example

The results for each control indicator composition and Indicator Composition 9 are shown in Table 3a and Table 9, respectively.

After the addition of chromium potassium sulfate to the control composition, each of the colorants except Congo red became colorless when exposed to hydrogen peroxide plasma as described above. Congo red changed from red to brown, which is a significant change to be seen by the human eye.

Example 10 PPreparation of Indicator Compositions using Cupric Acetate

Indicator compositions were prepared as described in Example 3 except a drop of cupric acetate salt solution containing 1 g of salt to 3.25 g of water was added to the initial composition and shaken in a glass vial. The colorants used are listed in Table 10.

Indicator compositions and control indicator compositions were coated on plastic backings and sterilized as described in Example 1.

The results for each control indicator composition B and Indicator Composition 10 are shown in Table 3a and Table 10, respectively.

After the addition of cupric acetate to the control composition, the colorants listed in Table 10 became almost colorless, significantly lighter, or lighter except Xylidine ponceau 2R when exposed to hydrogen peroxide plasma as described above. Xylidine ponceau 2R did not change color with the addition of cupric acetate and exposure to hydrogen peroxide plasma.

Example 11 Preparation of Indicator Compositions with Cupric Acetate and Device

Indicator compositions were prepared by dissolving 0.3 g of colorant in 90 ml of water. The colorants are listed in Table 11. The resulting solution was divided equally into 3 boats. A control indicator was made by immersing an 11 cm circle of Whatman Grade 1 filter paper in the solution, allowing the excess solution to drip from the paper, and drying for approximately 1 hour. The color of the dried control is recorded in Table 11.

A second solution (Indicator Composition 11) was prepared by adding 1.0 g of a cupric acetate {Cu(C₂H₃O₂)₂.H₂O} (available from Mallinckrodt, Inc., Hazelwood, Mo.) to 13 ml of water.

Five ml of the second solution was added to the solution in each boat. Three more 11 cm circles of filter paper were immersed one in each boat, allowed to drip and dried like the control. The color of the dried colorant and metallic salt composition is recorded in Table 11.

Adhesive (3M VHB acrylate adhesive on a release liner) was applied by transfer of the adhesive from the release liner to one side of each dried filter paper. A 1.9 cm (0.75 inch) circle was cut from the adhesive backed filter paper. The smaller adhesive circle was applied to the center of a 5.08 cm square (2 inch) by 0.25 millimeter (0.01 inch) thick piece of TYVEK type 10 1025 D spunbond olefin backing, available from E. I. du Pont de Nemours and Company, Wilmington, Del. The circle was enclosed within a device in the following manner. A 5.08 cm (2 inch) square by 0.25 mm (0.01 inch) thick piece of polyvinyl chloride (available as PJN-9708623 from Perfecseal, Minneapolis, Minn.) having a central 2.54 cm (1 inch) square by 0.95 cm (⅜ inch) deep vapor head space was glued using, Loctite 411 instant adhesive, to the spunbond backing.

Test Method

The devices were processed in the STERIS SYSTEM 1 sterilizer, obtained from STERIS Corporation, Mentor, Ohio. The devices were sealed in the sterilizer and exposed to a preliminary wash with an anticorrosive buffer solution. Sixty (60) ml of 35 percent liquid peracetic acid was then introduced to the buffer solution and circulated throughout the sterilization chamber for 12 minutes at 50-56° C. The circulating sterilant had a liquid peracetic acid concentration of 0.2 percent and a pH of 6.4. The sterilant was then drained and the sterilizing chamber was washed with water four times. The devices were removed and examined visually for color changes. The results are recorded in Table 11. Some of the devices changed color on the edges of the circle, but retained the initial color in the center. New indicator devices were tested without applying an adhesive coating to the back of the colored filter paper. The results of Examples 11-13 are noted in Tables 11, 12, and 13.

Example 12 Preparation of Indicator Compositions with Copper Sulfate and Devices

Indicator compositions were prepared as for Example 11. The colorants used are listed in Table 12. The second solution (Indicator Composition 12) was prepared by adding 1.0 g of copper sulfate (CuSO₄.5H₂O) (available from Mallinckrodt, Inc., Hazelwood, Mo.) to 13 ml of water. Devices were prepared and tested as described in Example 11. The results are recorded in Table 12.

Example 13 Preparation of Indicator Compositions with Cobalt Acetate and Devices

Indicator compositions were prepared as for Example 11. The colorants used are listed in Table 13. The second solution (Indicator Composition 13) was prepared by adding 1.0 g of cobalt(II) acetate tetrahydrate {Co(C₂H₃O₂)₂.4H₂O} (available from Sigma-Aldrich Fine Chemicals, St. Louis, Mo.) to 13 ml of water. Devices were prepared and tested as described in Example 11. The results are recorded in Table 13.

TABLE 1a Control Indicator Composition A Colorants and Results after Sterilization Color Index Initial Color without Color Change in No. Colorant Colorant Class Number Metallic Salts Sterilizer 1 ¹Alphazurine A Methane 42080 Blue/green None 2 ¹Azocarmine G Diazine 50085 Purple/pink None 3 Victoria green S extra Not known Not known Green Colorless 4 ¹Methyl violet 2B Methane 42535 Purple None (Basic violet 1) 5 ¹Ethyl violet (Basic Methane 42600 Blue None violet 4) 6 ¹Alizarin violet 3R Anthraquinone 61710 Light lilac None 7 ¹Basic blue 41 Not known Not known Dark lilac Lighter 8 ⁴FD/C blue 1 Methane 42090 Light blue None 9 ¹Toluidine blue O Thiazine 52040 Violet Lighter (Basic blue 17 or Tolonium chloride) 10 ¹Nile blue A Oxazine 51180 Purple/blue None 11 ¹Quinaldine red Cyanine None Red/gray Slightly lighter 12 ¹Basic blue 3 Oxazine 51004 Blue/green None 13 ¹Acid black 24 Diazo 26370 Blue/black None 14 ¹Acid red 97 Diazo 22890 Orange None 15 ¹Cibacron brilliant red Monoazo Not known Pale pink None 3B 16 ¹Sulforhodamine B Xanthene 45100 Hot pink None 17 ¹Direct blue 71 Triazo 34140 Purple/black None 18 ¹Chromotrope 2B Monoazo 16575 Pink-beige None 19 ¹Brilliant blue R (Acid Methane 42660 Blue None blue 83 or Coomassie brilliant blue R) 20 ¹Amaranth Monoazo 16185 Pink/gray None 21 ¹Rhodanine 6G Xanthene 45160 Hot pink None 22 ⁵Brilliant cresyl blue Oxazine 51010 Blue None BB 23 ³D & C red No. 33 Monoazo 17200 Red lilac 24 ¹Bordeaux R Monoazo 16180 Light pink None 25 ¹Direct red 75 Diazo 25380 Pale pink None 26 ¹Acid violet 7 Monoazo 18055 Lilac None 27 ¹Acid violet 5 Monoazo 18125 Dark pink None 28 ¹Plasmocorinth B Monoazo 16680 Dark pink None 29 ¹Brilliant crocein Diazo 27290 Orange None MOO 30 ¹Methylene green Thiazine 52020 Pale blue/gray Pale pink/gray 31 ¹Methylene violet Diazine 50206 Pink None 3RAX 32 ¹Ponceau SS Diazo 27190 Pink/beige None 33 ¹Reactive black 5 Diazo 20505 Blue/black None 34 ²Basic red 15 Not known Not known Hot pink None 35 ³Acid green AX986 Not known Not known Lime green None 36 ¹Lissamine green B Methane 44090 Blue/green None (Acid Green 50 or Wool Green S) 37 ¹Erioglaucine Methane 42090 Blue/green None 38 ¹Violamine R Xanthene 45190 Light pink Pink/violet 39 ¹Brilliant black BN Diazo 28440 Dark gray None 40 ¹Arsenazo 111 Diazo None Dark lilac Lighter 41 ³Alkali blue 4B Methane 42750 Blue Slightly lighter 42 ³Coomassie violet R Methane 42650 Grey/blue None 150 43 ¹Acid blue 92 Monoazo 13390 Lilac Light violet 44 ¹Acid blue 29 Diazo 20460 Grey/blue None 45 ¹Xylidine ponceau 2R Monoazo 16150 Orange None 46 ¹Reactive blue 2 Anthraquinone 61211 Blue/gray None ¹Commercially available from Sigma-Aldrich Fine Chemicals, St. Louis, MO. ²Commercially available from Spectra, Kearny, NJ. ³Commercially available from ICN Biomedicals, Costa Mesa, CA. ⁴Commercially available from Warner-Jenkinson, St. Louis, MO. ⁵Commercially available from Kodak, Rochester, NY

TABLE 1b Indicator Composition 1 Colorants and Results after Sterilization Color Index Initial Color with Color Change in No. Colorant Colorant Class Number Color Cupric Chloride Sterilizer 1 ¹Alphazurine A Methane 42080 Blue/green Blue/green Almost colorless 2 ¹Azocarmine G Diazine 50085 Purple/pink Purple/pink Significantly lighter 3 Victoria green S Not known Not known Green Green Colorless extra 4 ¹Methyl violet 2B Methane 42535 Purple Purple Colorless (Basic violet 1) 5 ¹Ethyl violet (Basic Methane 42600 Blue Blue Colorless violet 4) 6 ¹Alizarin violet 3R Anthraquinone 61710 Light lilac Light lilac Lighter 7 ¹Basic blue 41 Not known Not known Dark lilac Dark lilac Colorless 8 ⁴FD/C blue 1 Methane 42090 Light blue Light blue Almost colorless 9 ¹Toluidine blue O Thiazine 52040 Violet Blue/gray Colorless (Basic blue 17 or Tolonium chloride) 10 ¹Nile blue A Oxazine 51180 Purple/blue Very Light blue, Light gray Almost Colorless 11 ¹Quinaldine red Cyanine None Red/gray Pale pink/gray Colorless 12 ¹Basic blue 3 Oxazine 51004 Blue/green Blue Colorless 13 ¹Acid black 24 Diazo 26370 Blue/black Blue/black Colorless 14 ¹Acid red 97 Diazo 22890 Orange Orange Colorless 15 ¹Cibacron brilliant Monoazo Not known Pale pink Pale pink No change red 3B 16 ¹Sulforhodamine B Xanthene 45100 Hot pink Hot pink Very light pink 17 ¹Direct blue 71 Triazo 34140 Purple/black Purple/black Slightly lighter 18 ¹Chromotrope 2B Monoazo 16575 Pink-beige Dark gray Beige 19 ¹Brilliant blue R Methane 42660 Blue Blue Colorless (Acid blue 83 or Coomassie brilliant blue R) 20 ¹Amaranth Monoazo 16185 Pink/gray Pink/gray No change 21 ¹Rhodanine 6G Xanthene 45160 Hot pink Hot pink Almost colorless 22 ⁵Brilliant cresyl Oxazine 51010 Blue Blue Colorless blue BB 23 ³D & C red No. 33 Monoazo 17200 Red Purple/pink Tan 24 ¹Bordeaux R Monoazo 16180 Light pink Light pink Slightly lighter 25 ¹Direct red 75 Diazo 25380 Pale pink Almost Colorless colorless 26 ¹Acid violet 7 Monoazo 18055 Lilac Lilac Very light lilac 27 ¹Acid violet 5 Monoazo 18125 Dark pink Light red Colorless 28 ¹Plasmocorinth B Monoazo 16680 Dark pink Light violet Colorless 29 ¹Brilliant crocein Diazo 27290 Orange Light red Very pale orange MOO 30 ¹Methylene green Thiazine 52020 Pale Pale blue/gray Colorless blue/gray 31 ¹Methylene violet Diazine 50206 Pink Pink Colorless 3RAX 32 ¹Ponceau SS Diazo 27910 Pink/beige Pink/beige Light purple/pink 33 ¹Reactive black 5 Diazo 20505 Blue/black Blue/black Beige 34 ³Basic red 15 Not known Not known Hot pink Hot pink Colorless 35 ²Acid green AX986 Not known Not known Lime green Lime green Tan 36 ¹Lissamine green B Methane 44090 Blue/green Blue/green Colorless (Acid Green 50 or Wool Green S) 37 ¹Erioglaucine Methane 42090 Blue/green Blue/green Colorless 38 ¹Violamine R Xanthene 45190 Light pink Pink/violet Very light pink 39 ¹Brilliant black BN Diazo 28440 Dark gray Dark gray No change 40 ¹Arsenazo 111 Diazo None Dark lilac Blue/black Almost colorless ¹Commercially available from Sigma-Aldrich Fine Chemicals, St. Louis, MO. ²Commercially available from Spectra, Kearny, NJ. ³Commercially available from ICN Biomedicals, Costa Mesa, CA. ⁴Commercially available from Warner-Jenkinson, St. Louis, MO. ⁵Commercially available from Kodak, Rochester, NY.

TABLE 2 Indicator Composition 2 Colorants and Results after Sterilization Color Index Color with Ferrous Color Change in No. Colorant Colorant Class Number Initial Color Chloride Sterilizer 1 ¹Alphazurine A Methane 42080 Blue/green Blue/green Colorless 2 ¹Azocarmine G Diazine 50085 Purple/pink Purple/pink Colorless 3 Victoria green S Not known Not known Green Green Colorless extra 4 ¹Methyl violet 2B Methane 42535 Purple Purple Colorless (Basic violet 1) 5 ¹Ethyl violet Methane 42600 Blue Blue Colorless (Basic violet 4) 6 ¹Alizarin violet 3R Anthraquinone 61710 Light lilac Light lilac Colorless 7 ¹Basic blue 41 Not known Not known Dark lilac Dark lilac Colorless 8 ⁴FD/C blue 1 Methane 42090 Light blue Light blue Colorless 9 ¹Toluidine blue O Thiazine 52040 Violet Blue/gray Colorless 10 ¹Nile blue A Oxazine 51180 Purple/blue Blue/green Colorless 11 ¹Quinaldine red Cyanine None Red/gray Pink/gray Colorless 12 ¹Basic blue 3 Oxazine 51004 Blue/green Blue/green Colorless 13 ¹Acid black 24 Diazo 26370 Blue/black Blue/black Colorless 14 ¹Acid red 97 Diazo 22890 Orange Orange Colorless 15 ¹Cibacron brilliant Monoazo Not known Pale pink Pale pink Colorless red 3B 16 ¹Sulforhodamine B Xanthene 45100 Hot pink Hot pink Colorless 17 ¹Direct blue 71 Triazo 34140 Purple/black Purple/black Significantly lighter 18 ¹Chromotrope 2B Monoazo 16575 Pink-beige Pink-beige Colorless 19 ¹Brilliant blue R Methane 42660 Blue Blue Colorless (Acid blue 83 or Coomassie brilliant blue R) 20 ¹Amaranth Monoazo 16185 Pink/gray Pink/gray Significantly lighter 21 ¹Rhodanine 6G Xanthene 45160 Hot pink Hot pink Colorless 22 ⁵Brilliant cresyl Oxazine 51010 Blue Blue Colorless blue BB 23 ³D & C red No. 33 Monoazo 17200 Red Red Colorless 24 ¹Bordeaux R Monoazo 16180 Light pink Light pink Significantly lighter 25 ¹Direct red 75 Diazo 25380 Pale pink Pale pink Colorless 26 ¹Acid violet 7 Monoazo 18055 Lilac Lilac Colorless 27 ¹Acid violet 5 Monoazo 18125 Dark pink Dark pink Colorless 28 ¹Plasmocorinth B Monoazo 16680 Dark pink Brown Colorless 29 ¹Brilliant crocein Diazo 27290 Orange Orange Colorless MOO 30 ¹Methylene green Thiazine 52020 Pale blue/gray Pale blue/gray Colorless 31 ¹Methylene violet Diazine 50206 Pink Pink Colorless 3RAX 32 ¹Ponceau SS Diazo 27190 Pink/beige Pink/beige Colorless 33 ¹Reactive black 5 Diazo 20505 Blue/black Blue/black Colorless 34 ²Basic red 15 Not known Not known Hot pink Hot pink Colorless 35 ³Acid green Not known Not known Lime green Lime green Colorless AX986 36 ¹Lissamine green Methane 44090 Blue/green Blue/green Colorless B (Acid Green 50 or Wool Green S) 37 ¹Erioglaucine Methane 42090 Blue/green Blue/green Colorless 38 ¹Violamine R Xanthene 45190 Light pink Pink/Violet Colorless 39 ¹Brilliant black BN Diazo 28440 Dark gray Dark gray Colorless 40 ¹Arsenazo 111 Diazo None Dark lilac Dark gray Colorless ¹Commercially available from Sigma-Aldrich Fine Chemicals, St. Louis, MO. ²Commercially available from Spectra, Kearny, NJ. ³Commercially available from ICN Biomedicals, Costa Mesa, CA. ⁴Commercially available from Warner-Jenkinson, St. Louis, MO. ⁵Commercially available from Kodak, Rochester, NY

TABLE 3a Control Indicator B Colorants and Results after Sterilization Color Index Initial Color without Color Change in No. Colorant Colorant Class Number Metallic Salts Sterilizer 1 ¹Azocarmine G Diazine 50085 Purple/pink None 2 ¹Ethyl violet (Basic Methane 42600 Dark purple/blue None violet 4) 3 ¹Victoria pure blue Methane 42595 Blue None BO (Basic blue 7) 4 ¹Nile blue A Oxazine 51180 Lilac Slightly lighter 5 ¹Quinaldine red Cyanine None Muddy pink Light pink 6 ³Patent blue violet Methane None Green/blue None 7 ¹Acid fuchsin Methane 42685 Hot pink Lighter sodium salt 8 ¹Eriochrome black T Monoazo 14645 Light muddy pink None 9 ¹Eriochrome blue Monoazo 14640 Muddy pink None black B 10 ¹Aniline blue Methane 42780 Blue Gray/green 11 ¹Azure B Thiazine 52010 Blue Significantly lighter 12 ¹Guinea green B Methane 42085 Green Almost colorless (Acid green 3) 13 ⁴D & C green No. 5 Anthraquinone Not known Pale green None 14 ⁴Keystone soap Not known Not known Light green None fluoro green 15 ¹Congo red Diazo 22120 Red None 16 ¹Acid blue 113 Diazo 26360 Blue/gray None 17 ¹Acid red 151 Diazo 26900 Pink None 18 ¹Arsenazo 1 Monoazo None Light pink Slightly lighter 19 ¹Methylene violet Diazine 50206 Pink None 3RAX 20 ¹Mordant brown 48 Monoazo 11300 Very light orange None 21 ²Basic red 14 Not known Not known Pink Slightly lighter 22 ²Basic red 15 Not known Not known Pink Slightly lighter 23 ¹Fast green FCF Methane 42053 Green None 24 ¹Erioglaucine Methane 42090 Green/blue None 25 ³Alkali blue 4B Methane 42750 Blue Slightly lighter 26 ³Coomassie violet R Methane 42650 Grey/blue None 150 27 ¹Acid blue 92 Monoazo 13390 Lilac Light violet 28 ¹Acid blue 29 Diazo 20460 Grey/blue None 29 ¹Xylidine ponceau Monoazo 16150 Orange None 2R 30 ¹Reactive blue 2 Anthraquinone 61211 Blue/gray None ¹Commercially available from Sigma-Aldrich Fine Chemicals, St. Louis, MO. ²Commercially available from Spectra, Kearny, NJ. ³Commercially available from ICN Biomedicals, Costa Mesa, CA. ⁴Commercially available from Keystone Aniline Corp., Chicago, IL.

TABLE 3b Indicator Composition 3 Colorants and Results after Sterilization Color Index Color with Cobalt Color Change No. Colorant Colorant Class Number Initial Color Chloride in Sterilizer 1 ³Patent blue Methane None Green/blue Green/blue Colorless violet 2 ¹Aniline blue Methane 42780 Blue Blue Colorless 3 ¹Congo red Diazo 22120 Dark orange Dark orange Colorless 4 ¹Arsenazo 1 Monoazo None Light Pink Grey Colorless 5 ¹Acid blue 92 Monoazo 13390 Lilac Lilac Colorless 6 ¹Acid blue 29 Diazo 20460 Gray/blue Gray/blue Colorless ¹Commercially available from Sigma-Aldrich Fine Chemicals, St. Louis, MO. ²Commercially available from Spectra, Kearny, NJ. ³Commercially available from ICN Biomedicals, Costa Mesa, CA.

TABLE 4 Indicator Composition 4 Colorants and Results after Sterilization Color Index Color with Cobalt Color Change in No. Colorant Colorant Class Number Initial Color Acetate Sterilizer 1 ¹Nile blue A Oxazine 51180 Lilac Lilac Colorless 2 ¹Eriochrome Monoazo 14640 Muddy pink Light violet Colorless blue black B 3 ⁴D & C green Anthraquinone Not known Light green Light green Colorless No. 5 4 ²Basic red 15 Not known Not known Pink Pink Colorless 5 ¹Erioglaucine Methane 42090 Green/blue Green/blue Colorless 6 ¹Reactive blue 2 Anthraquinone 61211 Blue/gray Blue/gray Colorless ¹Commercially available from Sigma-Aldrich Fine Chemicals, St. Louis, MO. ²Commercially available from Spectra, Kearny, NJ. ³Commercially available from ICN Biomedicals, Costa Mesa, CA. ⁴Commercially available from Keystone Aniline Corp., Chicago, IL.

TABLE 5 Indicator Compositios 5 Colorants and Results after Sterilization Color Index Initial Color with Cupric Color Change in No. Colorant Colorant Class Number Color Chloride Sterilizer 1 ¹Azocarmine G Diazine 50085 Rose Light rose Colorless 2 ¹Victoria pure blue Methane 42595 Blue Dank blue Colorless BO (Basic blue 7) 3 ¹Acid fuchsin Methane 42685 Hot pink Pink Colorless sodium salt 4 ⁴D & C green No. 5 Anthraquinone Not known Pale green Very pale green Colorless 5 ⁴Keystone soap Not known Not known Light green Light green Colorless fluoro green 6 ²Basic red 14 Not known Not known Pink Pink Colorless ¹Commercially available from Sigma-Aldrich Fine Chemicals, St. Louis, MO. ²Commercially available from Spectra, Kearny, NJ. ³Commercially available from ICN Biomedicals, Costa Mesa, CA. ⁴Commercially available from Keystone Aniline Corp., Chicago, IL.

TABLE 6 Indicator Composition 6 Colorants and Results after Sterilization Colorant Color Index Color with Color Change No. Colorant Class Number Initial Color Cupric Sulfate in Sterilizer 1 ²Patent blue Methane None Green/blue Green/blue Green/gray violet 2 ¹Azure B Thiazine 52010 Blue Blue Clear 3 ¹Guinea green B Methane 42085 Green Green Mottled green on clear (Acid green 3) 4 ¹Methylene Diazine 50206 Pink Pink Almost colorless violet 3RAX 5 ²Basic red 15 Not known Not known Pink Pink Significantly lighter 6 ¹Fast green FCF Methane 42053 Green Green Mottled green on clear ¹Commercially available from Sigma-Aldrich Fine Chemicals, St. Louis, MO. ²Commercially available from Spectra, Kearny, NJ.

TABLE 7 Indicator Composition 7 Colorants and Results after Sterilization Color Index Color with Ferrous Color Change in No. Colorant Colorant Class Number Initial Color Chloride Sterilizer 1 ¹Azocarmine G Diazine 50085 Rose Light rose Colorless 2 ¹Victoria pure Methane 42595 Blue Dark blue Colorless blue BO (Basic blue 7) 3 ¹Acid fuchsin Methane 42685 Hot pink Pink Colorless sodium salt 4 ⁴D & C green Anthraquinone Not known Pale green Very pale green Colorless No. 5 5 ⁴Keystone soap Not known Not known Light green Light green Colorless fluoro green 6 ²Basic red 14 Not known Not known Pink Pink Colorless ¹Commercially available from Sigma-Aldrich Fine Chemicals, St. Louis, MO. ²Commercially available from Spectra, Kearny, NJ. ³Commercially available from ICN Biomedicals, Costa Mesa, CA. ⁴Commercially available from Keystone Aniline Corp., Chicago, IL.

TABLE 8 Indicator Composition 8 Colorants and Results after Sterilization Colorant Color Index Color with Color Change in No. Colorant Class Number Initial Color Ferrous Sulfate Sterilizer 1 ²Patent blue Methane None Green/blue Green/blue Significantly. Lighter violet 2 ²Eriochrome Monoazo 14645 Light muddy pink Light brown Colorless black T 3 ¹Eriochrome Monoazo 14640 Muddy pink Pale pink Colorless blue black B 4 ¹Acid blue 113 Diazo 26360 Blue/gray Blue/gray Colorless 5 ¹Acid red 151 Diazo 26900 Pink Pink Almost Colorless 6 ³Alkali blue 4B Methane 42750 Blue Blue Significantly. lighter ¹Commercially available from Sigma-Aldrich Fine Chemicals, St. Louis, MO. ²Commercially available from Spectra, Kearny, NJ. ³Commercially available from ICN Biomedicals, Costa Mesa, CA.

TABLE 9 Indicator Composition 9 Colorants and Results after Sterilization Color with Colorant Color Index Chromium Color Change in No. Colorant Class Number Initial Color Potassium Sulfate Sterilizer 1 ¹Ethyl violet (Basic Methane 42600 Dark Dark purple/blue Colorless violet 4) purple/blue 2 ¹Quinaldine red Cyanine None Muddy pink Muddy pink Colorless 3 ¹Eriochrome black T Monoazo 14645 Very light Light muddy pink Colorless muddy pink 4 ¹Eriochrome blue Monoazo 14640 Muddy pink Muddy pink Colorless black B 5 ¹Congo red Diazo 22120 Red Red Brown 6 ¹Acid blue 113 Diazo 26360 Blue/gray Blue/gray Colorless ¹Commercially available from Sigma-Aldrich Fine Chemicals, St. Louis, MO.

TABLE 10 Indicator Composition 10 Colorants and Results after Sterilization Color Index Color with Cupric Color Change in No. Colorant Colorant Class Number Initial Color Acetate Sterilizer 1 ¹Acid red 151 Diazo 26900 Pink Very pale pink, almost Lighter clear 2 ¹Mordant brown 48 Monoazo 11300 Very Light Cream Lighter Orange 3 ³Coomassie violet R Methane 42650 Gray/blue Purple Almost colorless 150 4 ¹Acid blue 29 Diazo 20460 Purple Pale purple Lighter 5 ¹Xylidine ponceau Monoazo 16150 Orange Yellow None 2R 6 ¹Reactive blue 2 Anthraquinone 61211 Blue/gray Blue/gray Slightly lighter ¹Commercially available from Sigma-Aldrich Fine Chemicals, St. Louis, MO. ²Commercially available from Spectra, Kearny, NJ. ³Commercially available from ICN Biomedicals, Costa Mesa, CA.

TABLE 11 Indicator Composition 11 Colorants and Results after Sterilization Colorant Color Index Color with Cupric No. Colorant Class Number Initial Color Acetate Color Change in Sterilizer 1 Evans blue Diazo 23860 Bright blue Bright blue Muddy light purple 2 Acid violet 7¹ Monoazo 18055 Magenta Very dark pink Pale yellow with a slightly pink center 3 Naphthol blue Diazo 20470 Navy blue Dark blue Dark purple black 4 Reactive black 5¹ Diazo 20505 Blue Blue Pink* 5 Brilliant black Diazo 28440 Dark blue Dark blue Off-white with light blue BN¹ center 6 Brilliant black Diazo 28440 Dark blue Dark blue Off-white* BN¹ 7 Azocarmine B Diazine 50090 Fuchsia Tan Yellow with a purple center 8 Azocarmine B Diazine 50090 Fuchsia Tan Yellow* *Indicator without adhesive ¹Commercially available from Sigma-Aldrich Fine Chemicals, St. Louis, MO.

TABLE 12 Indicator Composition 12 Colorants and Results after Sterilization Colorant Color Index Color with Cobalt No. Colorant Class Number Initial Color Acetate Color Change in Sterilizer 1 Cibacron brilliant Monoazo 18105 Fuchsia Fuchsia Muddy yellow-green with a red 3B¹ pink center 2 Evans blue Diazo 23860 Bright blue Bright blue Muddy brown with a slightly blue center 3 Reactive black 5¹ Diazo 20505 Blue Blue Pale blue with white edges 4 Reactive black 5¹ Diazo 20505 Blue Blue Pale spotty blue with white edges* 5 Brilliant black BN¹ Diazo 28440 Dark blue Dark blue Muddy light brown with slightly blue center *Indicator without adhesive ¹Commercially available from Sigma-Aldrich Fine Chemicals, St. Louis, MO.

TABLE 13 Indicator Composition 13 Colorants and Results after Sterilization Colorant Color Index Color with Cupric No. Colorant Class Number Initial Color Sulfate Color Change in Sterilizer 1 Evans blue Diazo 23860 Bright blue Bright blue Dark Blue 2 Acid violet 7¹ Monoazo 18055 Magenta Magenta Pale pink 3 Acid violet 7¹ Monoazo 18055 Magenta Magenta Pale yellow* 4 Naphthol blue black Diazo 20470 Navy blue Navy blue Muddy magenta with tan spots* 5 Reactive black 5¹ Diazo 20505 Blue Blue Dark pink 6 Brilliant black BN¹ Diazo 28440 Dark blue Dark blue Slight lighter blue 7 Azocarmine B Diazine 50090 Fuchsia Coral Purple *Indicator without adhesive. ¹Commercially available from Sigma-Aldrich Fine Chemicals, St. Louis, MO.

The complete disclosures of the patents, patent documents, and publications cited herein are incorporated by reference in their entirety as if each were individually incorporated. Various modifications and alterations to this invention will become apparent to those skilled in the art without departing from the scope and spirit of this invention. It should be understood that this invention is not intended to be unduly limited by the illustrative embodiments and examples set forth herein and that such examples and embodiments are presented by way of example only with the scope of the invention intended to be limited only by the claims set forth herein as follows. 

1. A peracetic acid sterilization indicator comprising a substrate and an indicator composition disposed thereon, wherein the indicator composition comprises: at least one salt, comprising cupric acetate; at least one colorant that changes color when exposed to peracetic acid; and at least one binder resin; wherein the colorant is selected from the group consisting of Acid violet 7, Evans blue, Naphthol blue black, Reactive black 5, Brilliant black BN, Azocarmine B, and combinations thereof.
 2. The sterilization indicator of claim 1, wherein the indicator composition further comprises at least one colorant that does not change color when exposed to peracetic acid.
 3. A method of monitoring a peracetic acid sterilization process, the method comprising: providing a peracetic acid indicator comprising a substrate and an indicator composition of claim 1; providing an article to be stenlized; and exposing the indicator and the article to be sterilized to peracetic acid.
 4. The method of claim 3, wherein the indicator composition further comprises at least one colorant that does not change color when exposed to peracetic acid.
 5. A peracetic acid sterilization indicator comprising a substrate and an indicator composition disposed thereon, wherein the indicator composition comprises: at least one salt, comprising cobalt acetate; at least one colorant that changes color when exposed to peracetic acid; and at least one binder resin; wherein the colorant is selected from the group consisting of cibacron brilliant red 3B, Evans blue, Reactive black 5,Brilliant black BN, and combinations thereof.
 6. The peracetic acid indicator of claim 5, wherein the indicator composition further comprises at least one colorant that does not change color when exposed to peracetic acid.
 7. A method of monitoring a peracetic acid sterilization process, the method comprising: providing a peracetic acid indicator comprising a substrate and an indicator composition of claim 5; providing an article to be sterilized; and exposing the peracetic acid indicator and the article to be sterilized to peracetic acid.
 8. The method of claim 7, wherein the indicator composition further comprises at least one colorant that does not change color when exposed to peracetic acid.
 9. A peracetic acid sterilization indicator comprising a substrate and an indicator composition disposed thereon, wherein the indicator composition comprises: at least one salt comprising cupric sulfate; at least one colorant that changes color when exposed to peracetic acid; and at least one binder resin; wherein the colorant is selected from the group consisting of Acid violet 7, Evans blue, Naphthol blue black, Reactive black 5, Brilliant black BN, Azocarmine B, and combinations thereof.
 10. The peracetic acid indicator of claim 9, wherein the indicator composition further comprises at least one colorant that does not change color when exposed to peracetic acid.
 11. A method of monitoring a peracetic acid sterilization process, the method comprising: providing a peracetic acid indicator comprising a substrate and an indicator composition of claim 9; providing an article to be sterilized; and exposing the peracetic acid indicator and the article to be sterilized to peracetic acid.
 12. The method of claim 11, wherein the indicator composition further comprises at least one colorant that does not change color when exposed to peracetic acid. 